CN107982517B - Western medicine compound composition for treating myocardial ischemia type chronic heart failure - Google Patents
Western medicine compound composition for treating myocardial ischemia type chronic heart failure Download PDFInfo
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- CN107982517B CN107982517B CN201711353242.9A CN201711353242A CN107982517B CN 107982517 B CN107982517 B CN 107982517B CN 201711353242 A CN201711353242 A CN 201711353242A CN 107982517 B CN107982517 B CN 107982517B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/164—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/15—Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
Abstract
The scheme relates to a western medicine compound composition for treating myocardial ischemia type chronic heart failure, which comprises saflufenafin, mannatide and fluvoxamine. Under the condition of achieving the same treatment effect, the compatibility of the three medicines greatly reduces the dosage of each medicine, thus obviously reducing the adverse reaction of the saflufenafin, relieving the depression of patients with heart failure and enhancing the immune function of the patients.
Description
Technical Field
The invention relates to a pharmaceutical composition, in particular to a western medicine compound composition for treating myocardial ischemia type chronic heart failure.
Background
Heart failure is the leading cause of death from cardiovascular disease. With the aging of China society and the increasing number of people with cardiovascular diseases such as hypertension and coronary heart disease, the incidence of heart failure is higher and higher. Chronic Heart Failure (CHF) is the result of the development of many chronic cardiovascular diseases, with great risks to the patient's life and poor prognosis.
In clinical research, the chronic heart failure is defined as common cardiac syndrome, and the clinical manifestations of patients are dyspnea, physical weakness, nausea, hypomnesis, decline of physical function indexes and the like, the chronic heart failure can bring serious influence to the lives of the patients, if the chronic heart failure cannot be controlled and treated in time, the lives of the patients can be threatened, the incidence rate of the chronic heart failure is higher in people over 35 years old, other complications can occur, the life quality of the patients is reduced, the treatment mode of the chronic heart failure is continuously improved along with the deepening of the cognitive process of the chronic heart failure, in 40-60 th century, the heart failure treatment mainly adopts a heart-kidney mode, common medicaments are digitalis and diuretics, the 70-80 th generation is converted into a heart circulation mode, the main treatment is based on the cardiotonic and diuretic processes, vasodilators are used, the pre-load and post-load of the heart are reduced, the hemodynamics are improved, meanwhile catecholamines, non-catecholamine and non-digitalis intensive heart failure treatment is tried on the basis of the heart failure, the 90 th generation, the blood vessel dilator produces a satisfactory treatment mode along with the development of the clinical development, the clinical development of the receptor is not satisfied, the angiotensin receptor is β, and the angiotensin receptor antagonist can be used for the patient, the patient can not be treated by the new angiotensin, and the new angiotensin receptor is obtained, the new angiotensin-used, the new angiotensin receptor is obtained by the new angiotensin.
Disclosure of Invention
Aiming at the technical problems in the prior art, the scheme provides a western medicine compound composition for treating myocardial ischemia type chronic heart failure, and aims to provide a pharmaceutical composition for jointly treating myocardial ischemia type chronic heart failure with small dosage, definite curative effect and few adverse reactions for people.
In order to achieve the purpose, the scheme is achieved through the following technical scheme:
a compound western medicine composition for treating myocardial ischemia type chronic heart failure is prepared from saflufenafin, mannatide, fluvoxamine and pharmaceutically acceptable adjuvants.
Preferably, the western medicine compound composition for treating myocardial ischemia type chronic heart failure is prepared from the following components in parts by weight, wherein the weight ratio of the saflufenafin to the mannatide to the fluvoxamine is 0.2-20: 0.2-1: 1.
preferably, the western medicine compound composition for treating myocardial ischemia type chronic heart failure is prepared from 3-10 parts by weight of camphorsulifene, mannatide and fluvoxamine: 0.4-0.8: 1.
preferably, the western medicine compound composition for treating myocardial ischemia type chronic heart failure is prepared from the following components in parts by weight: 0.5: 1.
preferably, the western medicine compound composition for treating myocardial ischemia type chronic heart failure is prepared from one or more of the following pharmaceutically acceptable auxiliary materials: lactose, carboxymethyl cellulose, corn starch, magnesium stearate, talcum powder and polyvinylpyrrolidone.
Preferably, the western medicine compound composition for treating myocardial ischemia type chronic heart failure is tablet, capsule or granule.
An application of a western compound composition for treating myocardial ischemia type chronic heart failure in preparing a medicament for treating myocardial ischemia type chronic heart failure is provided.
The saflufenacil is a short-acting ganglion blocking agent, has a blocking effect on sympathetic ganglia, and enables the pre-ganglionic fiber impulse not to reach the postganglionic fiber, so that the tension of peripheral sympathetic nerves is reduced, the effect of reducing blood pressure is achieved, and the function of directly expanding peripheral blood vessels is achieved; fluvoxamine is a selective 5-hydroxytryptamine reuptake inhibitor (SSRI) type antidepressant, inhibits the reuptake of 5-HT by rhodochrous neurons, but does not influence the reuptake of NA, has the advantages of no obvious effects of sedation, choline resistance and histamine resistance, safety, effectiveness and good tolerance, and is suitable for treating the depressed state of a patient with chronic heart failure; the mannan peptide is used for treating hypoimmunity, relieving side effects on hematopoietic system in clinical treatment stage, and has the advantages of rapid and complete absorption, and can be used by organism after absorption and participate in metabolism activity of organism.
The invention has the beneficial effects that:
1) can be used for treating myocardial ischemia type chronic heart failure. In the statistics of the results of the Left Ventricular Systolic Pressure (LVSP), the left ventricular diastolic pressure, the left ventricular end diastolic pressure and the maximum value of the change rate of the left ventricular pressure, the compound group of the invention has a significant difference (P < 0.01) compared with the model group, and has a significant difference (P < 0.05) or a significant difference (P < 0.01) compared with the single drug groups (the saflufenafin group, the fluvoxamine group and the mannan peptide group), which indicates that the compound drug of the invention has a synergistic effect on the treatment of the rat model with myocardial ischemia type chronic heart failure.
(2) Under the condition of achieving the same treatment effect, the compatible use of the three medicines greatly reduces the dosage of each medicine, thus obviously reducing the adverse reaction of the saflufenafin, relieving the depression of patients with heart failure and enhancing the immune function of the patients.
(3) The invention provides a new candidate drug for the search of the treatment of myocardial ischemia type chronic heart failure patients, and enriches the prior art.
Detailed Description
The present invention is further described in detail below with reference to examples so that those skilled in the art can practice the invention with reference to the description.
EXAMPLE 1 preparation of Compound tablet
And a proper amount of 5% PVP in absolute ethyl alcohol.
The preparation method comprises the following steps: firstly, the saflufenafin, the mannatide and the fluvoxamine are put into a mortar for grinding and mixing uniformly, the corn starch and the carboxypropyl methyl cellulose are added in sequence for mixing uniformly, the absolute ethyl alcohol solution of 5 percent PVP is used as a bonding agent for granulation, drying is carried out at 40 ℃, the granules are sized, the talcum powder is added for mixing uniformly, and tabletting is carried out, thus obtaining the oral liquid.
EXAMPLE 2 preparation of Compound tablet
The preparation method comprises the following steps: the preparation method comprises the steps of putting the saflufenafin, the mannatide and the fluvoxamine into a mortar, grinding and mixing uniformly, adding the lactose and the talcum powder, mixing uniformly, granulating by using 5% starch slurry as a bonding agent, drying at 40 ℃, granulating, adding the magnesium stearate, mixing uniformly, and tabletting.
EXAMPLE 3 preparation of Compound Capsule
The preparation process comprises the following steps: firstly, placing the saflufenafin and the mannatide into a mortar for grinding and mixing uniformly, adding the carboxypropyl methyl cellulose, the magnesium stearate and the polyvinylpyrrolidone in sequence for mixing uniformly, finally adding the fluvoxamine for mixing uniformly, and filling a capsule shell to obtain the oral liquid.
Example 4 Effect of the Compun Antrodine/mannatide/Fluvoxamine on myocardial ischemia type Chronic Heart failure rats
1. Preparation and administration of chronic myocardial ischemia heart failure model
140 male SD rats weighing 180-220 g. Animals were randomized into 7 groups: sham group (20); model group (20), heart failure caused by ligation of left coronary artery; in the camphorsulifene group (20), the camphorsulifene treatment is given after the left coronary artery is ligated; fluvoxamine group (20), treatment with fluvoxamine was given after ligation of the left coronary artery; mannatide group (20), administration of mannatide treatment after left coronary artery ligation; compound I (20), after left coronary artery ligation, certain dose of camphorsulifene, mannatide and fluvoxamine are administered for treatment; compound II group (20), the left coronary artery was ligated and then given a dose of acesulfame, mannatide and fluvoxamine. An animal model of heart failure was established by ligating the left coronary artery approximately flush between the rat left atrial appendage and the pulmonary artery cone at the lower margin of the left atrial appendage, along with a small bundle of myocardial fibers. The sham operation group was only threaded and not ligated. The test substances shown in Table 1 were administered to each group after surgery by gavage in addition to normal feeding. Cardiac function was measured after 8 weeks of feeding.
TABLE 1 grouping and administration of laboratory animals
The other groups were still fed with nutritional feed during the administration period, except for the normal group, and the administration was continued for 4 weeks twice daily.
2. Measurement of hemodynamic index
The BL-420E biological function experiment system is applied to determine various indexes of the hemodynamics: heart Rate (HR), systolic pressure (SBP), diastolic pressure (DBP), mean arterial pressure (ABP), Left Ventricular Systolic Pressure (LVSP), Left Ventricular Diastolic Pressure (LVDP), Left Ventricular End Diastolic Pressure (LVEDP), maximum value of left ventricular pressure change rate (+ -dp/dtmax) and the like, and synchronously monitoring the limb II-lead electrocardiogram. All recordings started at 10min of stabilization after intubation of the rats.
The statistical results of the test data are shown in tables 2, 3 and 4 by taking P < 0.05 (significance) or P < 0.01 (extreme significance) as the mark of difference. After the left coronary artery ligation operation is carried out and the feeding is carried out for 6 weeks, 2 patients die in a sham operation group, 6 patients die in a model group, 2 patients die in a camphorsulphonedifen group, 4 patients die in a fluvoxamine group and 3 patients die in a mannan peptide group, and 1 patient die in a compound I group and 2 patients die in a compound II group respectively.
TABLE 2 comparison of cardiac function indices of rats of different groups
TABLE 3 comparison of cardiac function indices of rats of different groups
| Group of | n | LVSP(mmHg) | LVEDP(mmHg) |
| Artificial operation group | 18 | 192.2±23.7 | 8.5±1.2 |
| Model set | 14 | 135.2±25.4 | 42.7±5.2 |
| Camphorsulifen group | 18 | 138.3±28.1 | 37.3±3.6 |
| Fluvoxamine group | 16 | 146.2±20.9 | 42.7±4.4 |
| Mannatide group | 17 | 140.1±21.8 | 41.5±3.7 |
| Compound I group | 19 | 176.5±20.1*&#Δ | 16.2±3.1**&&##ΔΔ |
| Compound II group | 18 | 183.1±18.4**&#Δ | 19.5±5.6**&##ΔΔ |
In comparison with the set of models,*p is less than 0.05; in comparison with the set of models,**P＜0.01；
compared with the camphorsulphonimifen group,&p is less than 0.05; in comparison with the group of ivabradine,&&P＜0.01；
in comparison with the fluvoxamine group,#p is less than 0.05; compared with the group of clopidogrel,##P＜0.01；
compared with the mannan peptide group,Δp is less than 0.05; compared with the mannan peptide group,ΔΔP＜0.01。
TABLE 4 comparison of cardiac function indices of rats of different groups
In comparison with the set of models,*p is less than 0.05; in comparison with the set of models,**P＜0.01；
compared with the camphorsulphonimifen group,&p is less than 0.05; in comparison with the group of ivabradine,&&P＜0.01；
in comparison with the fluvoxamine group,#p is less than 0.05; compared with the group of clopidogrel,##P＜0.01；
compared with the mannan peptide group,Δp is less than 0.05; compared with the mannan peptide group,ΔΔP＜0.01。
while embodiments of the invention have been disclosed above, it is not limited to the applications listed in the description and the embodiments, which are fully applicable in all kinds of fields of application of the invention, and further modifications may readily be effected by those skilled in the art, so that the invention is not limited to the specific details without departing from the general concept defined by the claims and the scope of equivalents.
Claims (7)
1. A western medicine compound composition for treating myocardial ischemia type chronic heart failure is characterized by comprising saflufenafin, mannatide, fluvoxamine and pharmaceutically acceptable auxiliary materials.
2. The western compound composition for treating myocardial ischemic chronic heart failure according to claim 1, wherein the weight ratio of the saflufenafin, the mannatide and the fluvoxamine is 0.2-20: 0.2-1: 1.
3. the western compound composition for treating myocardial ischemic chronic heart failure according to claim 1, wherein the weight ratio of the saflufenafin, the mannatide and the fluvoxamine is 3-10: 0.4-0.8: 1.
4. the western compound composition for treating myocardial ischemic chronic heart failure according to claim 1, wherein the weight ratio of the saflufenafin, the mannatide, and the fluvoxamine is 4: 0.5: 1.
5. the western compound composition for treating myocardial ischemia type chronic heart failure according to claim 1, wherein the pharmaceutically acceptable auxiliary materials are selected from one or more of the following substances: lactose, carboxymethyl cellulose, corn starch, magnesium stearate, talcum powder and polyvinylpyrrolidone.
6. The western compound composition for treating myocardial ischemia type chronic heart failure according to claim 1, wherein the western compound composition is in the form of tablets, capsules or granules.
7. The use of the western compound composition for the treatment of myocardial ischemic chronic heart failure according to claim 1 in the preparation of a medicament for the treatment of myocardial ischemic chronic heart failure.
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| EP2392345A2 (en) * | 2002-07-18 | 2011-12-07 | Cytos Biotechnology AG | Hapten-carrier conjugates comprising virus like particles and uses thereof |
| CN102379877A (en) * | 2011-09-13 | 2012-03-21 | 南京正宽医药科技有限公司 | Western medicinal compound for preventing or treating myocardial ischemic chronic heart failure and application thereof |
| CN102697856A (en) * | 2012-05-24 | 2012-10-03 | 西北农林科技大学 | Trimetaphan camsilate and linseed oil nanoemulsion antihypertensive drug |
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